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Home , Anabolic steroid, Nandrolone acetate, Tetrahydrogestrinone

ACMD Advisory Council on the Misuse of

Annex for the ACMD Anabolic Report, A-F;

September 2010

1 Annex A – ACMD Membership

Current members of the Advisory Council on the Misuse of Drugs (ACMD)

Member Sector Professor Leslie Iversen Professor of , (ACMD Chair) Oxford University Dr Dima Abdulrahim Briefings Manager, National Treatment Association Lord Victor Adebowale Chief Executive, Turning Point Dr Jason Aldiss Veterinary Medicine and Public Health - Managing Director of Eville & Jones Ltd Mrs Gillian Arr-Jones Chief Pharmacist for the Care Quality Commission Mr Martin Barnes Chief Executive, Drugscope Dr Margaret Birtwistle Specialist General Practitioner, Senior Tutor – Education and Training Unit, St George’s Hospital and Forensic Medical Examiner Commander Simon Bray Commander, Metropolitan Police Dr Roger Brimblecombe - pharmacologist Ms Carmel Clancy Principal Lecturer for Mental Health and Addiction, Middlesex University Professor Ilana Crome Professor of Addiction Psychiatry, Keele University Ms Robyn Doran Mental Health Nurse and Director of Operations, North- West London Mental Health Trust Professor Simon Gibbons Professor of Phytochemistry (natural product chemistry), School of Pharmacy, University of London Mr Patrick Hargreaves Advisor for Drugs and , Durham County Council Education Department Ms Caroline Healy Children's Strategic Adviser Professor Raymond Hill Professor of Pharmacology, Imperial College London Mr David Liddell Director, Scottish Drugs Forum

2 Mr Hew Mathewson CBE Dentist and former President and Chair of the General Dental Council (2002 to 2009) Dr Fiona Measham Senior Lecturer in Criminology, University of Lancaster Mr Graham Parsons Pharmacist Mr Trevor Pearce Director of Enforcement, Serious Organised Crime Agency District Judge Justin Phillips District Judge, Drugs Court London Mr Richard Phillips Independent Consultant,

DCC Howard Roberts Former Deputy Chief Constable, Nottinghamshire Police Dr Mary Rowlands Consultant Psychiatrist in Substance Misuse, Exeter Ms Monique Tomlinson Freelance Consultant in Drugs Misuse Mr Arthur Wing Director, Surrey & Sussex Probation Trust

3 Annex B – Additional Expertise

Lucy Blackburn Department for Culture, Media and Dr Rob Dawson General Practitioner

Patrick Deller HM Customs and Excise Michael Evans-Brown Liverpool John Moores University Noel Gill Public Health Laboratory Service Roy Jones Turning Point Dr Les King Former Head of Drugs Intelligence Unit, Forensic Science Service Dr Andrew Kicman King’s College London Dr Pirkko Korkia University of Bedfordshire

Jim McVeigh Liverpool John Moores University Professor Geoff Phillips Retired Chemist

Ric Treble Government Laboratory Chemist Marion Walker Pharmacist, Berkshire Healthcare NHS Foundation Trust Dr Mike White Forensic Science Service

4 Departmental Representation

David Carter Medicines and Healthcare products Regulatory Agency

Mark Prunty Department of Health

Lynda Scammell Medicines and Healthcare products Regulatory Agency

Angela Scrutton Home Office

5 Annex C. Pharmacology and Chemistry

Within the UK, there are few currently licensed preparations containing anabolic steroids. and are available for male (where patients fail to produce sufficient testosterone). is licensed for but it is not recommended as a therapeutic agent for this purpose. Oxymethelone is also available on a named patient basis for the treatment of aplastic anaemia. Other anabolic steroids continue to be available as pharmaceutical preparations in many countries,and are relatively easy to obtain for non-medicinal purposes.

Anabolic steroids are supplied as tablets or capsules for swallowing () and in vials for (intramuscular administration). Testosterone preparations are also available for administration through the (transdermal), within the mouth itself (sublingual or buccal routes), or by implantation into the abdomen (as well as testosterone formulations for oral administration or ).

Non-pharmaceutical preparations of anabolic steroids are additionally available, marketed for body building purposes. These are not necessarily produced in accordance with Good Manufacturing Practice. Non- pharmaceutical water-based testosterone suspensions for injection into a muscle have been advertised and discussed on web sites. The testosterone will rapidly enter the systemic circulation following administration, as it is present in an aqueous rather than an oily injection vehicle. A relatively recent phenomenon is the availability of novel anabolic steroids sold as dietary supplements, which arose initially as ‘prohormones,’ as a consequence of the Dietary Supplements Health and Education Act passed by US Congress in 1994. Steroidal ‘dietary supplements’ were originally supplied in capsules as prohormones, so-called because, following their oral administration; they are converted within the body to the potent testosterone or nandrolone (and also to a relatively large proportion of inactive metabolites for excretion). These prohormones are , and their corresponding 19-nor analogues. In 2004, the USA Anabolic Control Act included isomers of androstenediol and androstenedione, and their 19-nor analogues amongst the list of anabolic steroids (but not ; DHEA). As a consequence, the availability of these prohormones appears to have dropped remarkably, judging by the decrease in the number of advertisements for these compounds on the Internet.

This is of little consequence, as the steroidal dietary market had rapidly evolved in that time to the supply of analogues of existing anabolic steroids and those that were never commercialised, many appearing to originate from China. Such steroids are sometimes now referred to as ‘Designer Steroids’. They have been marketed, presumably, as they can be exempt from existing statutory controls regarding the manufacture and supply of drugs and further not to violate existing patents. They are advertised on many bodybuilding web sites. Examples include prostanozolol and 1-testosterone. Some analogues also appear to rely on , following their administration, to activate

6 the compound, for example, and 6- methylandrostenedione.

There is a concern that some will also use these supplements, necessitating anti-doping accredited laboratories to expand their screens on a continuous basis. These steroids are not to be confused with the very few anabolic steroids that have been specifically supplied in an attempt to circumvent sports drug tests, such as (THG). The efficacy of these designer steroids/dietary supplements is not proven and they have not undergone drug safety tests, as must be performed rigorously in the pharmaceutical industry. It is unlikely that such products have any adverse effects that have not already been described in the literature regarding administration. It is possible, nonetheless, that eventually an analogue will be produced that will cause unexpected toxicity of an acute and severe nature to humans.

Figure 1- With respect to the structure of testosterone, some of the chemical modifications that have been introduced in an attempt to maximise the anabolic effects relative to the androgenic effects.

Chemistry and Pharmaceutical Preparations Oral activity of anabolic steroids can be conferred by substitution of the 17- alpha hydrogen, which can be replaced with an alkyl group, either methyl (- CH3) or ethyl (-C2H5), thus making the 17-alkylated anabolic steroids such as for example, , methandienone, and . Absorption occurs across the gut into the hepatic-portal vein, and thus to the liver, where compounds are converted into more water-soluble products for excretion. The presence of the alkyl function hinders this conversion process, allowing such steroids to remain biologically active and, thus, they continue to flow intact through the liver, entering into the systemic circulation. A attached to C-1 can also confer oral activity, as in methenolone or mesterolone.

Injectable preparations do not require a 17-alkyl group as they are administered into a muscle, so the steroid is then released directly into the systemic circulation, rather than first passing through the liver. To permit slow

7 release of the steroid from the injection site, the steroid is administered in an oily liquid. Usually, the hydroxyl group (-OH) on the D-ring of anabolic steroid has also been bonded to an acid moiety to form an ‘’ linkage, giving even better retention within the . These esterified steroids are thereby slowly released into the blood circulation, where esterases cleave the bond to yield the biologically active anabolic steroid. The include cyclohexylpropionate, decanoate, laurate and phenylpropionate for nandrolone; , cypionate, decanoate, enanthate, isocaproate, phenylpropionate, propionate and undecanoate for testosterone, undecylenate for and acetate for . The mechanism of action of esterified nandrolone and other anabolic steroids, and the effect of drug delivery systems on their biological activity have been studied by van der Vies, 19931. The duration of action of the esters depends upon the rate of absorption from the site of administration. This is dependent on the chain length of the acid moiety and also the formulation, being related to the of the derivatives between the oil used in the formulation and plasma. In general, the longer the chain length, the more slowly the preparation is released into circulation, thus prolonging the duration of action.

Conversion of Weaker to Testosterone A minor amount of testosterone is derived from the body biochemically converting weaker androgens secreted by the testis, ovary and adrenal cortex. These weaker androgens are secreted into the systemic circulation and then subsequently converted to testosterone by other organs and tissues by the process of metabolism. The weaker androgens, dehydroepiandrosterone (DHEA) and androstenedione are not only converted peripherally to testosterone but also to the even more potent 5- alpha-, often referred to simply as dihydrotestosterone or DHT. As a consequence of the relatively small amount of testosterone produced, the peripheral metabolism of weaker androgens to testosterone has much greater relevance in the female than in the male (Kicman, in press; Longcope, 1986).

Effects on Hair Follicles An obvious effect of androgens in the female is at , where the soft (vellus) hair in the skin of the pubic region and also in the armpits is targeted, being converted to the coarse (terminal) hair. In boys at puberty, terminal hair is also produced on the face, called beard hair follicles (‘whiskers’). In other regions such hair growth depends on a number of factors, such as race, sex, age, and the site of the follicles (Brooks, 1984). The development of beard hair follicles is one of the secondary sexual characteristics which are manifested during puberty in boys. Other androgenic effects include the enlargement of the larynx causing a deepening of the voice, an increase in activity and (CNS) effects (increased and ). Anabolic effects are the growth of and ; the stimulation of linear growth eventually ceasing due to the closure of the epiphyses. Women exposed to unnaturally large amounts of

1 van der Vies, J. (1993). Pharmacokinetics of anabolic steroids. Wiener medizinische Wochenschrift,1993,143(14–15), 366–368.

8 androgens, such as by the chronic use of anabolic steroids, will become hirsute and eventually undergo (the appearance of the male secondary sexual characteristics in the female). The development of beard follicles and the deepening of the voice are considered to be largely irreversible.

Medical Applications The potential of anabolic steroids as therapeutic agents to increase weight, body mass and strength is being revisited. Anabolic steroids may play a significant role in the treatment of (wasting of muscle, loss of weight and ) associated with HIV/AIDS, severe burns and renal failure, where nutrition and standard care have been ineffective (Basaria et al., 2001). Carefully designed clinical trials may eventually give the definitive answers as to the usefulness of anabolic steroids as medicines, and whether xenobiotic anabolic steroids offer any advantage over very large (supraphysiological) doses of testosterone to men. In the interim, it seems sensible to consider replacement therapy to men in a catabolic state, where there is a significant decrease in circulating testosterone associated with certain chronic diseases (severe burn or HIV/AIDS-associated wasting).

Mode of Action Anabolic steroids are thought to exert their actions by several different mechanisms (Kicman, 2008). These mechanisms include modulating androgen expression as a consequence of (i) directly affecting the topology (shape) of the and thus subsequent interaction with comodulators (mainly coactivators) and transcriptional activity and (ii) intra-cellular metabolism. Other mechanisms include (iii) an ‘anticatabolic’ effect by interfering with receptor expression; and (iv) by non- genomic, as well as by genomic pathways, in the brain resulting in behavioural changes.

Once an androgen docks to an androgen receptor in a , the receptor changes its shape into an ‘active’ conformation where it can then link to a specific site on DNA within a cell. In fact, two receptors can bind to this site, referred to as a homodimer, which amplifies the subsequent effect on the DNA. Other called coregulators then cluster around the receptors that are interacting with the DNA site (Heemers et al., 2007). This result in activation and a resultant alteration in cell function, growth or differentiation.

It is assumed that anabolic steroids with enhanced anabolic activity, for example nandrolone, and stanozolol, alter the shape of the active androgen receptor in a somewhat different way compared from that if testosterone had bound to the receptor (Feldkoren et al., 2005; Holterhus et al., 2002). The active receptors still bind to the DNA but there is a different interaction with the coregulators, thus affecting gene activation in a way that may enhance, or in some cases, suppress gene activation. An appealing hypothesis is that anabolic-androgenic dissociation can also occur due to interaction with various coregulators in different tissues; thus growth in muscle is stimulated as a result of interaction with particular coregulators but in

9 androgenic target tissues the interaction is with different coregulators to those in muscle. There is little data, as yet, to support such a hypothesis, but it is known that the androgen FHL2 is expressed predominantly in the myocardium of the and the epithelial cells of the (Muller et al., 2000), and a number of other androgen receptor coregulators appear to be enriched in certain tissues (Heemers and Tindall, 2007) 2. How an anabolic steroid may affect androgen receptor conformation and interaction with particular coregulators is of obvious interest, as such knowledge may eventually offer an additional mechanism for anabolic-androgenic dissociation. Anabolic-androgenic dissociation may also occur due to intracellular metabolism. For example, in several androgenic target tissues, testosterone is converted to DHT, which binds more strongly to the androgen receptor but, by contrast, the anabolic steroid nandrolone is converted to a product that binds more weakly to this receptor (Celotti et al., 1992; Toth et al., 1982). This conversion does not significantly occur in human skeletal muscle, as in this tissue there is a lack of a converting () called 5-alpha-reductase (Thigpen et al., 1993). Hence, in muscle, nandrolone retains a stimulating effect but in androgenic tissues its effect is weakened, for example, permitting more ‘muscle per whisker’.

It is possible, but remains to be proven, that anabolic steroids may also interfere with the action of . One action of glucocorticoids is to stimulate breakdown of protein in skeletal muscle for the production of glucose, principally this being due to a glucocorticoid called . Cortisol is produced naturally in the body and its production increases considerably when the body is physiologically stressed. Anabolic steroids may counteract the catabolic effect by interfering with expression at the gene level but this remains unproven (Hickson et al., 1990).

The endocrinology of skeletal muscle is highly complex and there is a delicate balance between synthesis and breakdown during growth, health, disease and ageing (Sheffield-Moore et al., 2004). It is this complexity that makes it challenging to resolve the significance of anabolic steroids as anabolic (and anti-catabolic) agents across the spectrum, from the healthy who desires faster recovery from arduous training schedules where cortisol may be somewhat raised to the patient with severe physical trauma, such as from a burn , where there is extreme hypercortisolaemia (very raised circulating cortisol) and hypoandrogaenemia (lowered circulating androgens).

The behavioural effects of androgens/anabolic steroids inmen and women include those concerning sexual behaviour, cognitive abilities, aggression and mood Androgen receptors mediate the effects of anabolic steroids in the mammalian brain; the expression of and oestrogen receptors may also be affected. Non-genomic pathways are important too, i.e. cellular pathways not involving the androgen receptor binding to DNA. Induction of aggression in animals, by administering anabolic steroids, appears to overlap with neural circuits underlying the regulation of aggression by endogenous

2 Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: A diversity of functions converging on and regulating the AR transcriptional complex. Endocrine Reviews 2007; 28:778-808.

10 androgens, these being systems utilising the substances GABA, serotonin and arginine vasopressin (Clark et al., 2003).

11 Annex D. Contamination of Medicinal Products and Dietary Supplements with Anabolic Steroids

Some products have been contaminated with APIs (Active Pharmaceutical Ingredients) such as anabolic steroids (e.g. methandienone and stanozolol) (Baume et al., 2006; Geyer et al., 2003; Geyer et al., 2008; Parr et al., 2007), centrally acting appetite suppressants (e.g. sibutramine and rimonabant) (Food and Drug Administration, n.d.a, Jung et al., 2006), (e.g. bumetanide and ) (Food and Drug Administration, n.d.a; Food and Drug Administration n.d.b; Hoggan et al., 2007) and drugs for (e.g. ) (Medicines and Healthcare products Regulatory Agency, 2009). Products have also been openly, albeit unlawfully, marketed as containing (Parr et al., 2008) (a β2 ) and dinitrophenol (an uncoupler of mitochondrial oxidative phosphorylation (Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment, 2003)). Moreover, some of these APIs were found to be present at high strength (Baume et al., 2006; Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment, 2003; Geyer et al., 2003; Geyer et al., 2008; Hoggan et al., 2007; Jung et al., 2006; Parr et al., 2007; Parr et al., 2008) (not all reports provided data on this parameter).

12 Annex E. Harmful effects of anabolic steroids

Background While the use of anabolic steroids has been associated (Alghabban, 2004; Porta, 2008) with a number of adverse effects on health this area remains poorly researched. Much of the data are derived from case reports/series and cross-sectional study designs that are observational in nature. Observational designs are likely to remain the mainstay for some time, due, in part, to the methodological, ethical and logistical constraints which preclude the use of randomised controlled trials (RCTs) that make use of the high-dose polydrug regimens common to this user group (Evans-Brown & McVeigh, 2009). Many of the studies completed to-date suffer from issues in relation to their design, execution and analysis leading to problems with internal validity and generalisability. This is compounded by the fact that many studies do not provide sufficient detail of the study design to allow a detailed analysis, and, subsequently, comparison across different studies. Issues identified include bias (notably selection bias and information bias) and confounding (Delgado- Rodríguez & Llorca, 2004; Elwood, 2007; Higgins & Altman, 2008; Jenicek, 1999; von Elm et al., 2007; Reeves et al., 2008; Rothman et al., 2008; Sackett, 1979; Vandenbroucke et al., 2007). Specifically:

i. A failure to systematically perform drug testing and analysis as part of the study and an over-reliance on self-reported drug use. There has been a failure to recognise the heterogeneous nature of this group including potential confounders.

ii. Inadequate recognition of the compound-specific effects of the drugs, including the degree to which they diverge from the effects mediated by endogenous testosterone. This issue is further compounded by the varied polydrug regimens employed by users and the subsequent failure to systematically record the drugs used, doses taken and duration of use.

iii. The failure to examine in detail whether adverse events (particularly those documented as case reports) are causally associated with use of these drugs (Alghabban, 2004; Porta, 2008).

iv. Many of the adverse effects are subjective self-reports by users which is likely to result in bias: notably sampling bias and information bias (e.g. recall bias). Data are seldom available on the validity of the measures used, with many studies measuring ‘soft’ data variables, including physical and psychological health through simple ‘tick-boxes’ rather than using validated scales and measurements.

v. The failure to take into account/examine the phenomenon of expectancy and placebo effects (Beedie et al., 2009; Benedetti, 2009; Kienle & Kiene, 1997; Moerman, 2002). vi. An over-reliance on case reports as evidence of the incidence of adverse effects and as causal relationships. Case reports are, rightly, the “first line of evidence” (Jenicek, 1999) and “highly sensitive in picking up novelty in a

13 qualitative way” however, they are “poorly specific as to quantitative confirmation” (Vandenbroucke, 1999). In this group the prevalence of use and extent of exposure is difficult to determine, making any inferences on incidence rates unlikely. Moreover, we are not aware of any reports that have compared these cases to the background incidence in the general population.

vii. A lack of adequately powered prospective cohort studies within this population.

Cardiovascular While there have been case reports of adverse effects on the cardiovascular system which the authors attribute to the use of anabolic steroids (e.g. Alhadad et al., 2010; Bispo et al., 2009; Clark & Schofield, 2005; Fisher et al., 1996; McCarthy et al., 2000; Wysoczanski et al., 2008), many of these are inadequately reported and have failed to report potential confounding factors.

Hypertension The data on anabolic steroid use and are conflicting. While some cross sectional studies have reported significant increases in in those using anabolic steroids (Cohen et al., 1988; Lenders et al., 1988; Kuipers et al., 1991; Grace et al., 2003; Urhausen et al., 2004), other studies have reported no increase (Hartgens et al., 1996; Hervey et al., 1976; Riebe et al., 1992; Sader et al., 2001; Lane et al., 2006; Krieg et al., 2007; Urhausen et al., 1989; Karila et al., 2003). Further, some of the studies that reported significant increases in blood pressure found that mean blood pressure was below (Lenders et al., 1988; Grace et al., 2003) that defined as hypertension (Beevers et al., 2007; National Institute for Health and Clinical Excellence, 2006). Freed & Banks (1975) found a significant increase in systolic blood pressure in a cross-over trial using a single oral anabolic steroid (methandienone); Hartgens et al., (2003) in a prospective study found no significant increase in blood pressure as compared to non-using controls either at baseline or after 8 weeks of using high-dose self-directed regimens. Differences in the study design, participants and drug regimens could account for these findings.

While self-reported ‘high blood pressure’ is a relatively common finding in questionnaire-based studies e.g. 33.6% (n=110) (Korkia & Stimson, 1993), 36.4% (n=386) (Lenehan et al., 1996) these are subjective measures. A diagnosis of hypertension is not made subjectively (National Institute for Health and Clinical Excellence, 2006).

Lipid metabolism Data from cross-sectional studies have typically found that high density lipoprotein (HDL) is significantly decreased during anabolic steroid use (Ebenbichler et al., 2001; Lane et al., 2006; Sader et al., 2001). This is supported by a prospective study (Hartgens et al., 2004) and data from clinical trials using lower doses of injectable testosterone esters (Singh et al., 2002). The effects appear to be dependent on the type(s) of anabolic steroid, dose, duration of use and (Bhasin et al., 1996; Singh et

14 al., 2002). Moreover, it appears that some oral 17α-alkylated steroids have greater effects on reducing HDL than injectable testosterone ester products (Friedl et al., 1990; Thompson et al., 1989).

The data on anabolic steroid use and low-density lipoprotein (LDL) are conflicting. Although some cross-sectional studies have found a significant increase in LDL in anabolic steroid users (Glazer, 1991), this is not a consistent finding (Ebenbichler et al., 2001; Lane et al., 2006; Sader et al., 2001). Clinical trials using 600 mg/week of injectable testosterone enantate have not found this effect (Singh et al., 2006). Again these effects appear to be dependent on the type(s) of anabolic steroid, dose, duration of use and route of administration.

In a prospective study Hartgens et al., (2004) found an apparently beneficial significant decrease in lipoprotein (a) (which is an independent risk factor for ). However this effect was only found in those using high-dose polydrug regimens. In cross-sectional studies Cohen et al., (1996) reported a significant decrease in lipoprotein (a) while Palatini et al., (1996) reported no significant difference compared to controls.

Overall it appears that lipid metabolism normalises after drug cessation, although the length of time this takes appears to vary and be dependent on drugs used, doses taken and duration of use (Hartgens et al., 2004). Further research is required to gain a better understanding of the effects of anabolic steroids on lipid metabolism in users.

Cardiac structure & function Some cross-sectional studies have found no differences between anabolic steroid users and non-using controls in measured parameters Salke et al., 1985; Thompson et al., 1992); while others have observed some significant differences (Climstein et al., 2003; Dickerman et al., 1997; Karila et al., 2003; Urhausen et al., 1989; Yeater et al., 1996) such as increased left ventricular mass (Karila et al., 2003). While some prospective studies have found no differences in measured parameters (Hartgens et al., 2003, Palatini et al., 1996; Spataro et al., 1992; Zuliani et al., 1989), others have reported some significant differences (e.g. Piccoli et al., 1991; Sachtleben et al., (1993). Currently the data available are equivocal. Differences in the study design, methods, participants and drug regimens could account for these findings.

Vascular structure & function There are limited data on vascular structure and function in steroid users. The data that are available from cross-sectional studies is conflicting. Sader et al., (2001) found that while ’high-level’ bodybuilding is associated with impaired vascular reactivity and increased arterial thickening, the use of [anabolic steroids] per se is not associated with significant abnormalities of arterial structure or function” (including endothelial dysfunction). Lane et al., (2006), however, found that while endothelial-dependent dilation was not impaired compared to controls, endothelial-independent dilation was significantly impaired. Conversely, Ebenbichler et al., (2001) found that endothelial-

15 dependent dilation (indicating endothelial dysfunction) was significantly impaired compared to controls, where as endothelial-independent dilation was not. Differences in the study design, methods, participants and drug regimens could account for these findings.

Insulin resistance There are limited data on the effects of anabolic steroids on resistance. The data that are available from cross-sectional studies is conflicting. Lane et al., (2006) in a cross-sectional study of anabolic steroid users found no change in blood glucose or insulin levels. Cohen & Hickman (1987) found in their cross-sectional study that powerlifters using steroids had a diminished glucose tolerance which they believed to be secondary to , although according to the authors this did not meet the criteria for impaired glucose tolerance according to current guidelines. Singh et al., (2002) in a double-blind randomised controlled trial in healthy young men which administered a replacement dose of 600 mg/week of testosterone enantate over 20 weeks found no change in insulin resistance.

Other cardiovascular markers There are limited data on the effects of anabolic steroids on other markers associated with cardiovascular dysfunction. The data that are available from cross-sectional studies is conflicting.

Ebenbichler et al., (2001) and Graham et al., (2006) measured homocysteine levels in a cross-sectional study of steroid users. Although plasma homocysteine was found to be significantly increased compared to non-users these were within the reference interval (Antoniades et al., 2009; Refsum et al., 2004). Interestingly in the Graham et al., study (2006), those abstinent from steroid use for the past three months also had significantly higher homocysteine levels compared to bodybuilding and sedentary controls that reported never using anabolic steroids, these were also within the reference interval. Neither study reported adequate details on potential confounding factors that are known to affect homocysteine levels (Refsum et al., 2004). Zmuda et al., (1997) found no significant increase in plasma homocysteine levels in weightlifters treated with [a low dose] 200 mg/week of testosterone enantate for 3 weeks.

In a double-blind randomised controlled trial in healthy young men which administered a replacement dose of 600 mg/week of testosterone enantate for 20 weeks, Singh et al., (2002) found no significant changes in C-reactive protein (a marker of inflammation) compared to those participants receiving lower doses of testosterone.Overall, differences in the study design, methods, participants and drug regimens could account for these findings.

Haemostatic system There are limited data on the effects of anabolic steroids on the haemostatic system. Lane et al., (2006) in a cross-sectional study found no statistically significant differences in prothrombotic factors (of those measured) compared to users who had abstained for three months, bodybuilders who denied current/prior use of anabolic steroids, and healthy sedentary controls.

16 Alén (1985) and Baker et al., (2006) have reported significant increases in haematocrit, compared to controls, in cross-sectional studies of steroid users; 51% and 55.7% respectively (the reference interval is 45–52% for males). The haematocrit levels in the study by Baker et al., (2006) were significantly increased compared to sedentary controls and bodybuilders who reported never using anabolic steroids. They were not significantly different from those who had reported abstinence from steroid use in the past three months.

Data from controlled clinical trials of testosterone enantate 600 mg/week have found that there is a dose-dependent stimulatory effect on erythropoiesis and concomitant increase in haemoglobin and haematocrit in both young (19–35 years) and older healthy males (60–75 years). However, the effect was more pronounced in older men and a haematocrit above 54% was not seen in the younger group (Coviello et al., 2008). While data are limited it is interesting to note that the mean age of the steroid users in the study by Baker et al., (2006) was 42.4±3.8 years and all reported using “various doses [of anabolic steroids] in cyclical fashion over the previous 20 years”. Differences in the study design, methods, participants and drug regimens could account for these findings.

Musculoskeletal There have been several case reports of damage to tendons/ligaments that the authors attribute to the use of anabolic steroid use. It is thought that this could be as a result of disproportionate growth of the muscle compared to the tendons/ligaments. There have also been case reports of (breakdown of muscle) attributed to anabolic steroid use (Braseth et al., 2001; Daniels et al., 2006; Farkash, 2009), although potential confounding factors have not been sufficiently examined.

Hepatic The use of some types of anabolic steroids, in particular the 17α-alkylated compounds, has been associated with hepatic dysfunction and disease in clinical populations (Foss & Simpson, 1959; Velazquez & Alter, 2004). While cross-sectional data on liver function appears to demonstrate that liver function can be impaired in some users, the extent of this has been questioned by Dickerman et al., (1999) who have suggested that many studies have failed to examine specific markers of liver function and hence could not distinguish between markers of and those of muscle damage secondary to high-levels of resistance exercise. Studies have not examined the effect of polydrug regimens used by this group, nor potential confounding factors. Prospective studies that examine specific markers of hepatic function in users are required. There have been a small number of case reports of benign liver tumours (Schumacher et al., 1999; Socas et al., 2005; Velazquez & Alter, 2004), (Cabasso, 1994), and (Gorayski et al., 2008; Velazquez & Alter, 2004) in anabolic steroid users.

17 Endocrine & Genitourinary Data from cross-sectional studies have found that self-reported gynaecomastia is relatively common (Lenehan et al., 1996). However, the measures used have not been validated. Gynaecomastia is the growth of the glandular breast tissue in males thought to be caused by an imbalance in the ratio of free oestrogen to testosterone (Braunstein, 2007; Eckman & Dobs, 2008). Estimates of prevalence in the general population range from 60% in pubertal boys, 19% in those aged 16–20, 33–41% in those aged 25–45 and 55–60% in those aged >50 years (Eckman & Dobs, 2008). In anabolic steroid users it is thought to be mediated through the increased peripheral aromatization of exogenous steroids to oestrogenic metabolites and/or alterations in the transport/binding of endogenous oestrogen and testosterone in the blood (Pugeat et al., 1981). However, many of the drugs commonly used by this group (such as , gonadotrophin, ) have also been associated with gynaecomastia (Braunstein, 2007; Eckman & Dobs, 2008). The [self-directed] use of selective oestrogen receptor modulators (particularly ) (Lenehan et al., 1996; Baker et al., 2006), and, increasingly, inhibitors (Cohen et al., 2007; Parkinson & Evans, 2006) that are taken as both prophylactics to, and, for the treatment of, gynaecomastia is relatively common in this group.

Data from clinical trials have demonstrated that high levels of exogenous anabolic steroids can suppress endogenous testosterone production and , although there is considerable variation in this effect depending, inter alia, on the type of steroid used (Grimes et al., 2007). This effect is currently being tested in clinical research for the use of testosterone esters as a (Grimes et al., 2007). What is believe to be a similar effect has been reported in case reports/series and cross-sectional studies of steroid users, being associated with transient testicular atrophy and (Boyadjiev et al., 2000; Drakeley et al., 2004; Gazvani et al., 1997; Jarow et al., 1990; Karila et al., 2004; Knuth et al., 1989; Lloyd et al., 1996; Menon, 2003; Moretti et al., 2007; Peña et al., 2003; Ritter et al., 2005; Turek et al., 1995). For some individuals it appears that it can take many months for endogenous testosterone production and to recover (Gazvani et al., 1997).

It is common for users to self-report increased libido during an “on” cycle (i.e. when using anabolic steroids). Conversely, during an “off” cycle users often report that libido is reduced (Bolding et al., 2002; Korkia & Stimson, 1993; Korkia et al., 1996; Lenehan et al, 1996; Grace et al., 2001; Midgley et al., 2000). Some report no changes in libido. The measures used have not been validated. Moss et al., (1993) reported that current anabolic steroid users reported significantly more sexual intercourse compared to former users and non-users. However, the majority of users in this study were using what would be regarded as low doses of anabolic steroids. Further, the composition (inc. dose) of the drugs were not quantified. Interestingly, in a that used a replacement dose of 600 mg/week of testosterone enantate for 20 weeks there were no changes in self-reported sexual activity and sexual desire (Sinha-Hikim et al., 2002).

18 It is possible that the reported reduced libido could be due to the suppression of endogenous testosterone production (anabolic steroid-induced hypogonadism) when ceasing use (although there is limited data on testosterone levels in users when ceasing a cycle). Users have self-reported erectile dysfunction both during “on” cycles and “off” cycles. Overall, this area of research has received little attention (Moss et al., 1993). It is relatively common that individuals report the use of human chorionic (Lenehan et al., 1996; Baker et al., 2006) that is taken as both prophylactics to, and, for the treatment of, anabolic steroid-induced hypogonadism.

Little data exists on the sexual health of this group. However, this issue (along with blood-borne virus transmission) needs to be viewed within the wider public health concerns of spread of sexually transmitted infections.

We are aware of two case reports of prostate in steroid users (Larkin, 1991; Roberts & Essenhigh, 1986); two cases of (Bryden et al, 1995; Martorana et al., 1999); and, one of Wilms’ tumor (Prat et al., 1977).

Dermatological & Hair In cross-sectional studies, large numbers of steroid users self-report (Bolding et al., 2002; Korkia & Stimson, 1993; Lenehan et al., 1996; Parkinson & Evans, 2006). The measures used have not been validated. A limited number of case reports have been published in which the authors attribute the use of anabolic steroids to severe forms of acne including or acne fulminans (Collins & Cotterill, 1995; Gerber et al., 2008 (see also (Evans-Brown et al., 2008)); Heydenreich, 1989; Merkle et al., 1990; Piérard, 1998; Mayerhausen et al., 1989; Walker & Parry, 2006).

Male pattern baldness has been shown to be androgen-dependent (Randall, 2004). It is conceivable that in those who are genetically predisposed to this form of , the use of certain types of steroids could accelerate the progression of hair loss. In cross-sectional questionnaire studies many users report “baldness/hair loss” (presumably scalp hair) (Korkia & Stimson, 1993; Lenehan et al., 1996; Grace et al., 2001). Conversely, many steroid users report increased growth of when using steroids (Korkia & Stimson, 1993; Lenehan et al., 1996). From the limited data available growth of maybe particularly pronounced in female users (Korkia et al., 1996; Strauss et al., 1985). Overall, the measures used have not been validated.

Psychological & Behavioral

Aggression and There has been a great deal of interest in the use of anabolic steroids and effects on aggression and violence. It is common for users to self-report increased ‘aggression’ when using anabolic steroids which they suggest they use instrumentally in training (Korkia & Stimson, 1993; Lenehan et al., 1996; Monaghan, 2001). The measures used have not been validated. However, there are “conflicts” and contradictions both across the population of users

19 and within users (Monaghan, 2001). In naturalistic studies there has been a failure to examine potential confounding factors including drug expectancy effects and social factors (such as lifestyle and occupation) (Mazur, 2005). Data from a placebo-controlled randomised trial that used 600 mg/week of testosterone enantate over 10 weeks in healthy young men found no significant changes between control and treatment in self- and observer-rated (‘significant other’) aggression and anger (Bhasin et al., 1996). Conversely, Pope et al., (2000) who examined the effect of increasing doses of testosterone cipionate also in a placebo-controlled trial, this time for 6 weeks up to a maximum of 6 weeks found that there appeared to be a few ‘responders’ in the treatment group, noting that ‘drug response was highly variable’. While there was a significant increase in scores and aggression scores this effect was not uniform. They conclude “testosterone administration, 600 mg/wk increased ratings of manic symptoms in normal men. This effect, however, was not uniform across individuals; most showed little psychological change, whereas a few developed prominent effects. The mechanism of these variable reactions remains unclear.” (Pope et al., 2000) (see also Mazur, 2005). Overall, differences in the study design, methods, participants and drug regimens could account for these findings. A systematic review of this subject concluded that there are currently insufficient data to decide on a causal link between anabolic steroid use and aggressive and violent behaviour.

Depression Data from cross-sectional studies suggests that some users self-report upon ceasing a cycle of steroid use, for example Lenehan et al., 1996 found that approximately 20% (n=386) reported this finding. However, there are limited data on this topic using validated scales for depression. Given that steroid use can suppress endogenous testosterone production, it is plausible that when stopping use of these drugs the resultant hypogonadism could cause disturbances to mood, including depression, similar to that seen in clinical populations with hypogonadism (Christiansen, 2004). However, this remains to be systematically examined in steroid users.

Dependence It is unclear whether anabolic steroids have the potential to cause . However, it has been suggested that they can induce psychological dependence in some individuals, although detailed data is limited. For some individuals it is possible that the benefits of steroid use (that include increased training capacity, increased strength, ‘enhanced appearance’, and feelings of well being) act as a strong reinforcer to continue/recommence use. It is has been suggested that this can be a particularly strong force during an “off” cycle or when ceasing use because of the low levels of endogenous testosterone (anabolic steroid-induced hypogonadism) although this remains to be examined and, currently, there are limited data on this area. Data from cross-sectional studies have found that some users self-report wanting more anabolic steroids when use is stopped (for example Lenehan et al., (1996) found 16.9% of users reporting this feeling). Using either semi/structured clinical interviews or self-completed questionnaires typically based on DSM-III-R/DSM IV symptoms, a number of

20 studies have examined this issue in users. Here three or more symptoms (consistent with a diagnosis of dependence) were reported by 14.3% (n=11/77) (Malone et al., 1995), 23% (n=23/100) (Copeland et al., 2000), 25% (n=22/88) Pope & Katz (1994), 26% (n=13/50) (Midgley et al., 1999), 32% (n=20/62)(Kanayama et al., 2009), 33% (n=68/206) (Perry et al., 2005), 57% (n=28/49) (Brower et al., 1991), 57% (n=12/21) (Gridley & Hanrahan, 1994). Further work is required to validate and determine both the utility and significance of these findings. Overall, differences in the study design, methods and participants could account for these different findings. It is also unclear how representative these groups are of the broader group.

Other Psychological & Behavioural effects The effects of the use of anabolic steroids on mental health are for the most part drawn from self-reported effects in cross-sectional studies. The measures used often have not been validated. There have also been a limited number of case reports. Reported effects include , ‘mood swings’, and insomnia. There have also been a few case reports of ; however it is difficult to determine causality in these cases. Data from a retrospective study of mortality in steroid users found that there was no significant difference between the rate of suicide between steroid users and a control group of non- steroid users (Petersson, 2006). However, overall there is limited data on psychological and behavioural effects.

Specific concerns for young people Adolescence is a complex time of physical, emotional and psychological development which is mediated, in part, by the endogenous equivalents of commonly used performance-enhancing drugs such as testosterone, growth hormone and insulin-like growth factor-1. The use of supraphysiological doses of these drugs during this time in development could, potentially, disrupt the normal pattern of growth and behavioural maturation. This is likely dependent on the specific drugs used, doses taken and duration of use, along with an individual’s stage of development. Indeed, early clinical use of anabolic steroids in young people did lead to virilization (see below for effects on females). Further, it has been suggested that use of anabolic steroids in young people whose growth plates in the long have not fused could lead to . While we are not aware of any such data in relation to illicit steroid use, testosterone esters have been used clinically in adolescent males in an attempt to reduce final height of those with constitutionally tall stature (Drop et al., 1998). Here the authors report that the doses that have been used “correspond to roughly 4 times the normal T production rate of adult men or to about 8–10 times that of early adolescence”, although the authors note that prospective controlled studies are required to determine if this treatment is effective in reducing final height.

Specific concerns for females Given the low endogenous levels of testosterone in females, any increase through endogenous sources (such as in disease states) and, by analogy, exogenous sources (i.e. anabolic steroids) can have marked physical effects, and can lead to virilisation which includes: , deepening of the voice, amenorrhoea/, clitoral enlargement, atrophy of breast tissue, and

21 changes in libido. The impact of these effects can be pronounced, and, in some cases, permanent. There are limited data in relation to these effects in female steroid users, due to the relatively small numbers of users and compounded by the clandestine nature of use amongst this sub population. Most data are derived from self-reports (Korkia et al., 1996; Strauss et al., 1985).

Injecting Background

Data from the United Kingdom suggests that the majority of users inject anabolic steroid (ranging from 59.6% (Bolding et al., 1999) to 89% (Grace et al., 2001), with most studies reporting that ≥70% inject (Burton, 1996; Grace et al., 2001; Korkia & Stimson, 1993; Lenehan et al., 1996; Pates & Barry, 1996). These figures include a majority that both inject and take oral drug products and a minority that exclusively use injectable products. Limited data are available on the routes of administration for the small number of female users, however it appears that many of these also inject (Korkia & Stimson, 1993; Korkia et al., 1996).

Individuals who inject are potentially at risk of a number of sequelae that include: 1. damage to the injection site as a result of poor injecting technique; 2. bacterial and fungal infections as a result of poor injecting technique, contaminated drug products, and sharing vials and/or reusing injecting equipment; and, 3. blood-borne viruses (BBV) such as HIV, B and hepatitis C as a result of sharing used injecting equipment (direct sharing) or reusing injecting equipment and, subsequently, sharing vials with others (indirect sharing).

Limited data are available on injecting practices in users within the UK (Baker et al., 2006; Burton, 1996; Evans, 1997; Grace et al., 2001; Korkia & Stimson, 1993; Lenehan et al., 1996; Midgley et al., 2000; Pates & Barry; 1996) (Table 1). Both studies conducted by Bolding et al., (1999; 2002) with gay/bisexual users in London gyms found no direct sharing (Bolding et al., 1999; Bolding et al., 2002). Other studies have found relatively low-levels of lifetime direct sharing: 0.3% (Lenehan et al., 1996), 2.1% (Midgley et al, 2000), 5.7% (Korkia & Stimson, 1993), 6% (Crampin et al., 1998); while Burton (1996) reported 16% and Grace et al., (2001) 20% “at times when they [syringes] were not readily available”. However, these latter papers do not provide data on the frequency of sharing (i.e. whether it was lifetime, last month, etc); it is unclear what is responsible for the large variation in reports of sharing between studies. A subset of these studies also examined indirect sharing, particularly through the use of multi-dose vials. This behaviour could be a source of infection, notably BBVs, if this co-occurs with the reuse of injecting equipment. Further, it is possible that the sharing of multi-dose vials (particularly in non-salubrious environments) where basic hygiene measures are not followed (and/or storage and handling measures for drug products are not adequate) could increase the risk of bacterial and fungal contamination. Although we are not aware of any research in relation to this context, data from clinical settings have suggested that contamination has taken place

22 leading to iatrogenic infections (Kirschke et al., 2003; Thompson et al., 2009; Vonberg & Gastmeier, 2007).

Korkia Leneh Pates Burton Cramp Boldin Midgel Grace Boldin & an et & (1996) in et g et y et et al., g et Stims al., Barry al., al., al., (2001) al., on (1996) (1996) (1998) (1999) (2000) (2002) (1993) ¶ ¶ “Ever” 5.7% 0.3% 1.74% 16% 6% 0% 2.1% 20% 0 shared (5/88) (1/386) (3/176) (8/134) (1/47) † Shared N/A N/A N/A N/A ≤1% N/A N/A N/A N/A last month (1/134)

“Ever” N/A* N/A N/A 59% N/A 9.9% 23.4% N/A 2.4% shared (8/81) (/47) (2/85) multi-dose vial (a)

“Ever” N/A N/A N/A 37% N/A 7.4% 4.2% N/A 8.2% reuse (6/81) (2/47) (7/85) injecting equipment (b)

Reporting N/A N/A N/A N/A N/A 3.7% 4.2% N/A 1.2% both (3/81) (2/47) (1/85) behaviours (a + b)

† “admitted to sharing, borrowing or passing on needles and syringes”. *There were anecdotal reports about the sharing of injecting equipment and of multi- dose vials. ¶ Study examined the use of anabolic steroids by gay/bisexual users. Table. Data on direct and indirect sharing in anabolic steroids users from UK studies.

Burton (1996) found that 59% of steroid injectors reported sharing multi-dose vials with other users and 37% having reused their ‘needles’, although no data are available on the co-occurrence of these two behaviours which would be required in order to pose a risk of transmission of infections. Data from three studies (see Table 1) have found these two behaviours in 3.7% (3/81) (Bolding et al., 1999), 4.2% (2/47) (Midgely et al., 2000), and 1.2% (1/85) (Bolding et al., 2002) of users. Again, no data on co-occurrence are reported.

Damage to the injection site There have been several case reports of peripheral neuropathy that the authors attribute to injecting anabolic steroids (Dickerman et al., 1997; Evans,

23 1997; Mondellie et al., 1998; Perry, 1994) or muscular hypertrophy leading to nerve compression (Dickerman et al., 2002). While the incidence of these sequelae are unknown, data from Larance et al., (2008) found that 10% (n=31) of users self-reported hitting a nerve when injecting (however, it is unclear how users determined this and how representative this group was). There has also been a small number of case reports of ‘pseudotumours’ (Khankhanian et al., 1992; Kienbacher et al., 2007; Weinreb et al., 2010). The aetiology of these could be due physical trauma from the injection process, a tissue reaction to the drug product or contaminant therein. Akhavani et al., (2006) reported a case of compartment syndrome in an anabolic steroid user which they believe was as a result of intramuscular injection of an anabolic steroid. Again, the incidence of such sequelae is unknown.

Bacterial and fungal infections There have been a small number of case reports of bacterial and fungal infections that the authors attribute to injecting anabolic steroids. Typically these have presented as localised infection such as abscesses (Al-Ismail et al., 2002; Bergman, 1993; Cooper et al., 1993; Dunn et al., 2002; Evans, 1997; Gautschi & Zellweger, 2006; Herr et al., 2002; Kienbacher et al., 2007; Krauss et al., 1995; Larsen & Halvorsen, 2000; Maropis & Yesalis, 1994; Marquis & Maffulli, 2006; Plaus & Hermann, 1991; Rastad et al., 1985; Rich et al., 1999). The aetiology of these infections could be due to poor injecting technique and/or contamination of injectable dosage forms (the latter of which could occur as a result of poor injecting technique, microbial contamination during manufacture/distribution (Evans-Brown et al., 2009) or sharing multi- dose vials). The incidence of these types of sequelae are unknown. Self- reported lifetime data from cross-sectional studies from Australia and the United States have found that 13% (n=100) (Peters et al., 1997) and 13% (n=60) (Larance et al., 2005) of users reported “buttock abscess” (Australia, face-to-face structured interviews); while Cohen et al., found that 7% (n=1,955 males) reported “infections resulting from injection” (US, Internet-based study). The lifetime report of “sore/swollen injection sites” was 57% (n=100) (Peters et al., 1997) and 45% (n=60) (Larance et al., (2005). “Pain at injection sites” was reported by 36.4% (39/111) by Bolding et al., (2002), although it is not clear if this was as a result of infection or trauma caused by the injecting process. Larance et al., (2008) found that 13% (n=31) of users reported an “infection that required treatment with antibiotics”; while 3% (n=31) reported “injection-related problem requiring hospitalisation”. The interpretation of these data is complicated by the use of different methodologies between studies and the lack of concurrent validity. Further it is unclear how representative these groups are of the broader user group. Aside from the three case reports list above (Evans, 1997; Dunn et al., 2002; Marquis & Maffulli, 2006), we are not aware of any further data from the United Kingdom.

Blood-borne viruses There are limited data in relation to the prevalence and transmission of BBVs in anabolic steroid users within the UK. There have been a small number of case reports from France and the United States that the authors attribute to the direct sharing of injecting equipment to HIV (Scott & Scott, 1989; Sklarek et al., 1984; Henrion et al., 1992), hepatitis B (Slarek et al., 1984) and

24 hepatitis C (Coton et al., 2000; Rich et al., 1998) infection. However, it is difficult to draw any firm conclusions from these data given aetiological confounding factors These cases do, however, demonstrate that direct sharing within this user group has taken place.

To our knowledge, the work of Crampin et al., (1998) is the only published study that has examined HIV and hepatitis B exposure in anabolic steroid users attending needle and syringe programmes (NSP) in the United Kingdom. They analysed data from 1991–1996 derived from the national Unlinked Anonymous HIV Prevalence Monitoring Survey of injecting drug users. Here they found that 2% (3/149) of users had evidence of previous or current hepatitis B infection, while none had antibodies to HIV. The study did not examine hepatitis C exposure. Since this time there has been significant epidemiological shifts in HIV and hepatitis C infection in the UK (Health Protection Agency Centre for Infections, 2006; Health Protection Agency Centre for Infections, 2008)). Data from Bolding et al., (2002) who studied anabolic steroid use in gay/bisexual users in London found that 36.7% (40/109) of those that had used steroids in the past year self-reported being HIV-positive (no participants reported direct sharing and the only individual to report both sharing multi-dose vials and reuse of injecting equipment self- reported as being HIV-negative. It is unknown if these two behaviours co- occurred (Bolding et al., 2002)). The number of HIV-positive individuals within these samples could be a reflection of both clinician-prescribed (Johns et al., 2005) and self-directed use (Mooney & Vergel, 2004) of anabolic steroids as a prophylactic/treatment for HIV/AIDS-related wasting.

While the risk of BBV transmission in anabolic steroid users appears to be low when compared to other groups, such as those injecting opiates and (Health Protection Agency, 2007), the practices and risks remain poorly characterised. Importantly, any such work that is undertaken must include those individuals who are not in contact with NSPs, as despite the extensive peer distribution network that appears to exists (Gilliver, 2007; McVeigh et al., 2007), their injecting practices may differ significantly from their peers who do attend NSPs. This is particularly relevant for younger users, where it has been reported that they will not attend NSPs for fear of being labelled as an injecting drug user (Personal communication to Michael Evans-Brown, 2008).

25 Annex F. Case Studies of Specific Services developed for Anabolic Steroid Users

1 Drugs in Sport Clinic and Users’ Support (DISCUS) The clinic started in 1994 with both specialist medical and nursing input and now has more than 1,000 patients registered. Alongside the NSP (where some users are collecting injecting equipment for up to 250 users), DISCUS provides testing for BBV and immunisation for hepatitis A and B, regular blood investigations, specialist dietary services (inc. body fat analysis), and referral to other services where necessary.

2 Smart Muscle (not currently operating) Smart Muscle builds upon the previous work of SUSSED which included specific interventions focussed on anabolic steroid use within the gay community. Part of the social care organisation Turning Point, Smart Muscle is a central London service that is free and confidential. It provides information on diet, training, cycles, stacks, post-cycle therapy, side effects and help to identify counterfeit drugs. Needle and syringe exchange (using pick-and-mix) is available to complete their course and advice is provided to ensure that their injection technique is correct (if they choose to inject). The service has a partnership with the local GUM service who offers liver function testing, vaccinations for hepatitis A and B, along with full sexual health screens. The service does refer clients to specialist services as required. In the last 18 months Smart Muscle has provided services to 299 users, from ages 18–70, with the majority of users aged 22–50. 70% of clients have identified themselves as gay or bisexual and 12 clients reported themselves as HIV positive.

3 Surrey Outreach Service Established in 1992, this project provides information, advice and health checks via a network of NSP and drop-in centre. However, the key innovative element of the approach is the use of specialist outreach workers to maintain close links with the anabolic steroid-using communities.

4 Wirral Harm Reduction Service Harm reduction services for anabolic steroid users in the Wirral have been available since the 1990s. The intervention is nurse-led incorporating NSP, harm reduction, general health checks, sexual health screening and specialist referrals as required.

26